Utility of Phospho-Histone H3 in Problematic Uterine Smooth Muscle Tumors
Adriana M Doldan-Silvero, Carlos R Acevedo-Gadea, Deborah Z Stevens, Richard Cartun, Srini Mandavilli. Hartford Hospital, Hartford, CT; Yale School of Medicine, New Haven, CT
Background: Phospho-histone H3 (PHH3), a mitosis specific immunomarker, has been suggested as a robust way of evaluating mitotic index (MI) in neoplasms wherein MI is important in accurate classification. MI is a key histologic feature in classifying uterine smooth muscle tumors but there are several confounding factors. There is only one pilot study that suggested PHH3 as usefu in separating smooth muscle tumors of uncertain malignant potential (STUMP) from leiomyosarcoma (LMS). No studies have been done evaluating the PHH3 usefulness in other smooth muscle tumors such as cellular/mitotically-active and atypical/ bizarre leiomyomas (CL-BL) ocasionally difficult to separate from STUMP and LMS. The aim of this study was to evaluate the utility of PHH3 immunolabeling in a group of morphologically challenging smooth muscle tumors.
Design: 9 cases of CL-BL, 6 of STUMP and 5 of LMS (1 myxoid LMS) from 2000 to 2012, previously diagnosed using the presently accepted morphologic criteria, were retrieved from the archives of the Department of Pathology at Hartford Hospital. Representative H&E slides were reviewed, PHH3 immunohistochemical stains were performed and positivity scored by 2 pathologists in the hot spot areas of staining as # positive cells/ 10 HPF (PHH3 MI). The mean MI of each group (CL-BL, STUMP and LMS) was then calculated.
|CL (n=9)||STUMP(n=6)||LMS (n=5)|
|MI||0-10 mitoses/10HPF (mean: 1.8)||0-10 mitoses/10HPF (mean: 4)||3-15 mitoses/10HPF (mean: 10)|
|Necrosis||Absent||Absent||Present in 4 out of 5 cases|
|Atypia||Mild (7) and moderate (2)||Moderate (3) and severe (3)||moderate (4) to severe (1)|
|PHH3 MI||0-11 mitoses/10HPF (mean: 4)||0-15 mitoses/10HPF (mean:6.5 )||5-30 mitoses/10HPF (mean: 12)|